Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation

Y. Ikeda, M. Handa, T. Kamata, K. Kawano, Y. Kawai, K. Watanabe, K. Kawakami, K. Sakai, M. Fukuyama, I. Itagaki, A. Yoshioka, Z. M. Ruggeri

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Abstract

We found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two- to three-fold increase in their intracellular concentration ([Ca2+](i)). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+](i) increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+](i) and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+](i) may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.

Original languageEnglish
Pages (from-to)496-502
Number of pages7
JournalThrombosis and Haemostasis
Volume69
Issue number5
DOIs
Publication statusPublished - 1993 Jan 1

ASJC Scopus subject areas

  • Hematology

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    Ikeda, Y., Handa, M., Kamata, T., Kawano, K., Kawai, Y., Watanabe, K., Kawakami, K., Sakai, K., Fukuyama, M., Itagaki, I., Yoshioka, A., & Ruggeri, Z. M. (1993). Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation. Thrombosis and Haemostasis, 69(5), 496-502. https://doi.org/10.1055/s-0038-1651640